User:Ivan E. Wang/Sandbox Reserved 895 - Revision history

Ivan E. Wang at 22:55, 24 April 2020

2020-04-24T22:55:47Z

←Older revision		Revision as of 22:55, 24 April 2020
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	== Enzymatic Activity of RPE65 ==		== Enzymatic Activity of RPE65 ==
	(PLACEHOLDER)		(PLACEHOLDER)
-	[[Image:~~Visual Cycle~~.jpg\|thumb\|right\|512 px\|alt=Figure 2: Human Visual Cycle\| Figure 2: The canonical Visual Cycle in Humans <ref>DOI 10.1016/j.bbadis.2018.04.014</ref>]]	+	[[Image:Visual_Cycle_RPE.jpg\|thumb\|right\|512 px\|alt=Figure 2: Human Visual Cycle\| Figure 2: The canonical Visual Cycle in Humans <ref>DOI 10.1016/j.bbadis.2018.04.014</ref>]]

Ivan E. Wang at 21:54, 3 March 2020

2020-03-03T21:54:52Z

←Older revision		Revision as of 21:54, 3 March 2020
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	<StructureSection load='4rsc' size='500' side='right' caption='Figure 1: Emixustat and palmitate bound in the active site of RPE65' scene=''>		<StructureSection load='4rsc' size='500' side='right' caption='Figure 1: Emixustat and palmitate bound in the active site of RPE65' scene=''>

-	Retinal pigment epithelium 65 (RPE65) also known as retinoid isomerohydrolase (IMH) is a 65 kDa enzyme located within the human retinal pigment epithelium (hRPE) cells. RPE65 is exclusively expressed within hRPE cells and is not expressed anywhere else within the body which makes RPE65 a useful drug target. ~~PRE65~~ is responsible for the chemical conversion of ''all-trans''-retinyl ester to ''11-cis''-retinol, the rate limiting step, in the canonical visual cycle.	+	Retinal pigment epithelium 65 (RPE65) also known as retinoid isomerohydrolase (IMH) is a 65 kDa enzyme located within the human retinal pigment epithelium (hRPE) cells. RPE65 is exclusively expressed within hRPE cells and is not expressed anywhere else within the body which makes RPE65 a useful drug target. RPE65 is responsible for the chemical conversion of ''all-trans''-retinyl ester to ''11-cis''-retinol, the rate limiting step, in the canonical visual cycle.

	</StructureSection>		</StructureSection>

Ivan E. Wang at 19:01, 25 February 2020

2020-02-25T19:01:25Z

←Older revision		Revision as of 19:01, 25 February 2020
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	= Medical Relevance =		= Medical Relevance =
-	(~~PLACEHOLDER~~)	+	== Dry (atrophic) age related macular degeneration ==
		+
		+	== Stargadt's Disease ==

	This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.		This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.

Ivan E. Wang at 18:57, 25 February 2020

2020-02-25T18:57:50Z

←Older revision		Revision as of 18:57, 25 February 2020
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	Classification nomenclature for RPE65 is as follow according to <insert classification type>		Classification nomenclature for RPE65 is as follow according to <insert classification type>

-	Retinal pigment epithelium 65 (RPE65) resembles a 7-bladed propeller with two deep binding pockets that contains a lipophilic binding pocket (which binds to endogenous palmitoyl acid) as well as an iron(II) atom stabilized by 5 histidine residues. (~~<insert histidine residue positions>~~)	+	Retinal pigment epithelium 65 (RPE65) resembles a 7-bladed propeller with two deep binding pockets that contains a lipophilic binding pocket (which binds to endogenous palmitoyl acid) as well as an charged iron(II) atom stabilized by 4 histidine residues (His180, His241, His313 and His527) which binds to the carboxylic acid functional group of endogenous palmitoyl acid.

Ivan E. Wang at 18:29, 25 February 2020

2020-02-25T18:29:06Z

←Older revision		Revision as of 18:29, 25 February 2020
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	= Introduction to the RPE65 =		= Introduction to the RPE65 =
	<StructureSection load='4rsc' size='500' side='right' caption='Figure 1: Emixustat and palmitate bound in the active site of RPE65' scene=''>		<StructureSection load='4rsc' size='500' side='right' caption='Figure 1: Emixustat and palmitate bound in the active site of RPE65' scene=''>
		+
	Retinal pigment epithelium 65 (RPE65) also known as retinoid isomerohydrolase (IMH) is a 65 kDa enzyme located within the human retinal pigment epithelium (hRPE) cells. RPE65 is exclusively expressed within hRPE cells and is not expressed anywhere else within the body which makes RPE65 a useful drug target. PRE65 is responsible for the chemical conversion of ''all-trans''-retinyl ester to ''11-cis''-retinol, the rate limiting step, in the canonical visual cycle.		Retinal pigment epithelium 65 (RPE65) also known as retinoid isomerohydrolase (IMH) is a 65 kDa enzyme located within the human retinal pigment epithelium (hRPE) cells. RPE65 is exclusively expressed within hRPE cells and is not expressed anywhere else within the body which makes RPE65 a useful drug target. PRE65 is responsible for the chemical conversion of ''all-trans''-retinyl ester to ''11-cis''-retinol, the rate limiting step, in the canonical visual cycle.

Line 6:		Line 7:

	= Structure and Activity =		= Structure and Activity =
-	== Structural Analysis of RPE65 ==	+	== Classification and Structural Analysis of RPE65 ==
-	(~~PLACEHOLDER~~)	+
		+	Classification nomenclature for RPE65 is as follow according to <insert classification type>
		+
		+	Retinal pigment epithelium 65 (RPE65) resembles a 7-bladed propeller with two deep binding pockets that contains a lipophilic binding pocket (which binds to endogenous palmitoyl acid) as well as an iron(II) atom stabilized by 5 histidine residues. (<insert histidine residue positions>)
		+

	== Enzymatic Activity of RPE65 ==		== Enzymatic Activity of RPE65 ==

Ivan E. Wang at 18:24, 25 February 2020

2020-02-25T18:24:36Z

←Older revision		Revision as of 18:24, 25 February 2020
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	<StructureSection load='4ryy' size='340' side='right' caption='Figure 3:(R)-emixustat and palmitate bound in the active site of RPE65' scene=''>		<StructureSection load='4ryy' size='340' side='right' caption='Figure 3:(R)-emixustat and palmitate bound in the active site of RPE65' scene=''>
	(''R'')-emixustat (ACU-4429) is an investigational small molecule inhibitor of RPE65 first invented by a British-American chemist, Ian L. Scott. Formulated as an hydrochloride salt, (''R'')-emixustat hydrochloride is taken by mouth and functions as a visual cycle modulator (VCM) to reduce toxic retinal byproducts in the canonical visual cycle such as A2E.		(''R'')-emixustat (ACU-4429) is an investigational small molecule inhibitor of RPE65 first invented by a British-American chemist, Ian L. Scott. Formulated as an hydrochloride salt, (''R'')-emixustat hydrochloride is taken by mouth and functions as a visual cycle modulator (VCM) to reduce toxic retinal byproducts in the canonical visual cycle such as A2E.
		+
	In 2008, Acucela Inc. partnered with Otsuka Pharmaceutical Company for the continued development of (''R'')-emixustat as a potential inhibitor of RPE65. Currently (''R'')-emixustat is in Phase III clinical trials in the United States for the potential treatment of Stargard's disease, a juvenile form of atrophic (dry) age dependent macular degeneration (AMD). Additionally, (''R'')-emixustat is investigated as potential therapy for diabetic retinopathy and diabetic macular edema.		In 2008, Acucela Inc. partnered with Otsuka Pharmaceutical Company for the continued development of (''R'')-emixustat as a potential inhibitor of RPE65. Currently (''R'')-emixustat is in Phase III clinical trials in the United States for the potential treatment of Stargard's disease, a juvenile form of atrophic (dry) age dependent macular degeneration (AMD). Additionally, (''R'')-emixustat is investigated as potential therapy for diabetic retinopathy and diabetic macular edema.
		+
	Historically (''R'')-Emixustat was tested as a possible treatment for dry (atrophic) age-related macular degeneration in Phase IIb/III clinical trials but failed to show clinical outcomes due to significant pharmacokinetic and pharmacodynamic short falls.		Historically (''R'')-Emixustat was tested as a possible treatment for dry (atrophic) age-related macular degeneration in Phase IIb/III clinical trials but failed to show clinical outcomes due to significant pharmacokinetic and pharmacodynamic short falls.

Ivan E. Wang at 18:23, 25 February 2020

2020-02-25T18:23:38Z

←Older revision		Revision as of 18:23, 25 February 2020
Line 1:		Line 1:
	= Introduction to the RPE65 =		= Introduction to the RPE65 =
	<StructureSection load='4rsc' size='500' side='right' caption='Figure 1: Emixustat and palmitate bound in the active site of RPE65' scene=''>		<StructureSection load='4rsc' size='500' side='right' caption='Figure 1: Emixustat and palmitate bound in the active site of RPE65' scene=''>
-	Retinal pigment epithelium 65 (RPE65) also known as retinoid isomerohydrolase is a 65 kDa enzyme located within the human retinal pigment epithelium cells. PRE65 is responsible for the chemical conversion of ''all-trans''-retinyl ester to ''11-cis''-retinol in the visual cycle.	+	Retinal pigment epithelium 65 (RPE65) also known as retinoid isomerohydrolase (IMH) is a 65 kDa enzyme located within the human retinal pigment epithelium (hRPE) cells. RPE65 is exclusively expressed within hRPE cells and is not expressed anywhere else within the body which makes RPE65 a useful drug target. PRE65 is responsible for the chemical conversion of ''all-trans''-retinyl ester to ''11-cis''-retinol, the rate limiting step, in the canonical visual cycle.

	</StructureSection>		</StructureSection>
Line 21:		Line 21:
	=== (''R'')-Emixustat (ACU-4429) ===		=== (''R'')-Emixustat (ACU-4429) ===
	<StructureSection load='4ryy' size='340' side='right' caption='Figure 3:(R)-emixustat and palmitate bound in the active site of RPE65' scene=''>		<StructureSection load='4ryy' size='340' side='right' caption='Figure 3:(R)-emixustat and palmitate bound in the active site of RPE65' scene=''>
-	(''R'')-emixustat (ACU-4429) is an investigational small molecule inhibitor of RPE65 first invented by a British-American chemist, Ian L. Scott. Formulated as an hydrochloride salt, (''R'')-emixustat hydrochloride is taken by mouth and functions as a visual cycle modulator (VCM) to reduce toxic retinal byproducts such as A2E.	+	(''R'')-emixustat (ACU-4429) is an investigational small molecule inhibitor of RPE65 first invented by a British-American chemist, Ian L. Scott. Formulated as an hydrochloride salt, (''R'')-emixustat hydrochloride is taken by mouth and functions as a visual cycle modulator (VCM) to reduce toxic retinal byproducts in the canonical visual cycle such as A2E.
	In 2008, Acucela Inc. partnered with Otsuka Pharmaceutical Company for the continued development of (''R'')-emixustat as a potential inhibitor of RPE65. Currently (''R'')-emixustat is in Phase III clinical trials in the United States for the potential treatment of Stargard's disease, a juvenile form of atrophic (dry) age dependent macular degeneration (AMD). Additionally, (''R'')-emixustat is investigated as potential therapy for diabetic retinopathy and diabetic macular edema.		In 2008, Acucela Inc. partnered with Otsuka Pharmaceutical Company for the continued development of (''R'')-emixustat as a potential inhibitor of RPE65. Currently (''R'')-emixustat is in Phase III clinical trials in the United States for the potential treatment of Stargard's disease, a juvenile form of atrophic (dry) age dependent macular degeneration (AMD). Additionally, (''R'')-emixustat is investigated as potential therapy for diabetic retinopathy and diabetic macular edema.
		+	Historically (''R'')-Emixustat was tested as a possible treatment for dry (atrophic) age-related macular degeneration in Phase IIb/III clinical trials but failed to show clinical outcomes due to significant pharmacokinetic and pharmacodynamic short falls.
		+
	</StructureSection>		</StructureSection>

Ivan E. Wang at 21:48, 4 February 2020

2020-02-04T21:48:24Z

←Older revision		Revision as of 21:48, 4 February 2020
Line 1:		Line 1:
-	=~~=Your Heading Here (maybe something like 'Structure')=~~=	+	= Introduction to the RPE65 =
-	<StructureSection load='~~1stp~~' size='~~340~~' side='right' caption='~~Caption for this structure~~' scene=''>	+	<StructureSection load='4rsc' size='500' side='right' caption='Figure 1: Emixustat and palmitate bound in the active site of RPE65' scene=''>
-	~~This~~ is a ~~default text~~ for ~~your page~~ '''~~Ivan E. Wang/Sandbox Reserved 895~~'''~~. Click above on~~ ''~~'edit this page''' to modify. Be careful with the < and > signs.~~	+	Retinal pigment epithelium 65 (RPE65) also known as retinoid isomerohydrolase is a 65 kDa enzyme located within the human retinal pigment epithelium cells. PRE65 is responsible for the chemical conversion of ''all-trans''-retinyl ester to ''11-cis''-retinol in the visual cycle.
-	~~You may include any references to papers as~~ in~~: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to~~ the ~~rescue~~.	+

-	~~== Function ==~~	+	</StructureSection>

-	== ~~Disease~~ ==	+	= Structure and Activity =
		+	== Structural Analysis of RPE65 ==
		+	(PLACEHOLDER)

-	== ~~Relevance~~ ==	+	== Enzymatic Activity of RPE65 ==
		+	(PLACEHOLDER)
		+	[[Image:Visual Cycle.jpg\|thumb\|right\|512 px\|alt=Figure 2: Human Visual Cycle\| Figure 2: The canonical Visual Cycle in Humans <ref>DOI 10.1016/j.bbadis.2018.04.014</ref>]]

-	== Structural highlights ==

-	~~This is a sample scene created with SAT to <scene name~~=~~"/12/3456/Sample/1">color</scene> by Group, and another to make <scene name~~=~~"/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.~~	+	= Protein-Ligand Interaction =
		+	== Endogenous Ligand ==
		+	(PLACEHOLDER)

		+	== Exogenous Ligand ==
		+	=== (''R'')-Emixustat (ACU-4429) ===
		+	<StructureSection load='4ryy' size='340' side='right' caption='Figure 3:(R)-emixustat and palmitate bound in the active site of RPE65' scene=''>
		+	(''R'')-emixustat (ACU-4429) is an investigational small molecule inhibitor of RPE65 first invented by a British-American chemist, Ian L. Scott. Formulated as an hydrochloride salt, (''R'')-emixustat hydrochloride is taken by mouth and functions as a visual cycle modulator (VCM) to reduce toxic retinal byproducts such as A2E.
		+	In 2008, Acucela Inc. partnered with Otsuka Pharmaceutical Company for the continued development of (''R'')-emixustat as a potential inhibitor of RPE65. Currently (''R'')-emixustat is in Phase III clinical trials in the United States for the potential treatment of Stargard's disease, a juvenile form of atrophic (dry) age dependent macular degeneration (AMD). Additionally, (''R'')-emixustat is investigated as potential therapy for diabetic retinopathy and diabetic macular edema.
	</StructureSection>		</StructureSection>
-	== ~~References~~ ==	+
		+	=== (''S'')-Emixustat ===
		+	<StructureSection load='4ryz' size='340' side='right' caption='Figure 4:(S)-emixustat and palmitate bound in the active site of RPE65' scene=''>
		+	(PLACEHOLDER)
		+	</StructureSection>
		+
		+	== ''R/S'' Enantiomers Differences ==
		+	(PLACEHOLDER)
		+
		+	= Disease Implications =
		+	(PLACEHOLDER)
		+
		+	= Medical Relevance =
		+	(PLACEHOLDER)
		+
		+	This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.
		+
		+	= References =
	<references/>		<references/>

Ivan E. Wang: New page: ==Your Heading Here (maybe something like 'Structure')== This is a default text for you...

2020-02-04T21:47:14Z

New page: ==Your Heading Here (maybe something like 'Structure')== <StructureSection load='1stp' size='340' side='right' caption='Caption for this structure' scene=''> This is a default text for you...

New page

==Your Heading Here (maybe something like 'Structure')==
<StructureSection load='1stp' size='340' side='right' caption='Caption for this structure' scene=''>
This is a default text for your page '''Ivan E. Wang/Sandbox Reserved 895'''. Click above on '''edit this page''' to modify. Be careful with the < and > signs.
You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.

== Function ==

== Disease ==

== Relevance ==

== Structural highlights ==

This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.

</StructureSection>
== References ==
<references/>